Neuroscience and Neurobiology Commons^™

Harmonious Healing: A Review Of Music Therapy, A Humanities-Based Approach To Alzheimer’S Disease Treatment, Rohan K. Desai

Kentucky Undergraduate Journal for the Health Humanities

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease often characterized by memory loss, confusion, and overall cognitive decline. The aging global population has, in recent years, highlighted the fundamental lack of pharmacological treatments for individuals facing an AD diagnosis. In response, a growing body of research has shifted focus to non-pharmacological humanities-based interventions. One such intervention has been music therapy (MT). Music-focused measures have shown great promise as a method of slowing cognitive decline, but mixed results in the literature warrant the need for further investigation. Often, socioeconomic barriers can limit an individual’s access to drug-related treatments, but the affordable …

High Volume Multiplex Staining Of Mouse Model In Alzheimer’S Associated Disease Pathology, Chloe Embry

Lewis Honors College Thesis Collection

Although neurodegenerative diseases are often clinically distinct, they typically share common pathological markers. One of the most common causes of clinical dementia is Alzheimer’s disease (AD). Pathologically, AD is defined by the presence of intercellular tangles composed of hyperphosphorylated tau proteins and extracellular plaques made of abnormally cleaved amyloid-beta proteins. However recent genome-wide association studies have also found that many of the predispositions for AD are located on or near genes highly expressed in microglia. In the healthy CNS, microglia act as the brain’s immune system and are chiefly involved in neuronal support and maintaining homeostasis throughout the CNS. Typically, …

Il-1r1 Within The Meningeal Lymphatic System, Nolan Abdelsayed

Lewis Honors College Thesis Collection

The meninges are made up of three membranes; the pia mater, arachnoid mater, and dura mater, that surround the brain and spinal cord. These specialized layers work in concert with cerebrospinal fluid (CSF), to protect the central nervous system by adding a layer of cushion and removing waste products from the CNS. Additionally, the meninges act as a physical barrier between the central nervous system and the periphery. The meningeal lymphatic system is a specialized group of vessels that lie within the meninges that assist in the flow of fluid and waste products from the brain. If the meningeal lymphatic …

Age- And Sex-Dependent Alterations In Primary Somatosensory Neuronal Calcium Network Dynamics During Locomotion, Sami L. Case

Theses and Dissertations--Pharmacology and Nutritional Sciences

Over the past 30 years, the calcium (Ca2+) hypothesis of brain aging has provided clear evidence that hippocampal neuronal Ca2+ dysregulation is a key biomarker of aging. Indeed, age-dependent Ca2+-mediated changes in intrinsic excitability, synaptic plasticity, and activity have helped identify some of the mechanisms engaged in memory and cognitive decline. However, much of this work has been done at the single-cell level, mostly in slice preparations, and in restricted structures of the brain. Recently, our lab identified age- and Ca2+-related neuronal network dysregulation in the cortex of the anesthetized animal. Still, investigations in the awake animal are needed to …

The Effects Of Extended Fructose Access On Relative Value And Demand For Fructose, Saccharin, And Ventral Tegmental Stimulation, Megan Halloran

Theses and Dissertations--Psychology

Globally, food addiction (FA) is a growing area of research and is largely attributed to the availability of foods that are both energy dense and high in fats and sugars. Further, it has been suggested, that sugar and fat, when consumed frequently, have properties similar to drugs of abuse. While the validity of FA is questioned, researchers have drawn parallels between substance use disorder (SUD) and FA. For example, sugar binge models emphasize craving, withdrawal and binging as primary components of FA, which are also hallmarks of SUD. Additionally, both natural rewards, like sugars, and drug rewards act on the …

Exploring The Molecular Basis Of Touch: A Comparative Analysis Of Gene Expression In Sensory Corpuscle-Rich And Corpuscle-Poor Skin Regions In The Duck, Thomas Hart

Theses and Dissertations--Biology

Cutaneous touch is facilitated by discrete cellular complexes composed of non-neuronal cells associated with mechanoreceptor neuron endings. The non-neuronal cells of these cutaneous end organ complexes (CEOCs) are believed to contribute to touch, but their role in touch sensation remains unclear. To better understand the function of CEOC cells, we sought to characterize the transcriptional profile of CEOC-rich tissue and identify genes expressed in CEOC cells. Bill skin of the tactile foraging Pekin duck (Anas platyrhynchos) is dense with CEOCs, specifically the avian analogs of mammalian Pacinian and Meissner corpuscles, while corpuscles in duck foot skin are scarce. Using RNA …

Alzheimer’S Disease Genetics And Short-Chain Fatty Acid Treatment In Studies Of The Murine Gut Microbiome, Diana Zajac

Theses and Dissertations--Physiology

Elucidating the relationship of the gut microbiome in Alzheimer's Disease (AD) risk and pathogenesis is an area of intense interest. Since 60 to 80% of AD risk is related to genetics and APOE alleles represent the most impactful genetic risk factors for AD, their mechanism(s) of action are under intense scrutiny.

First, I conducted a study on APOE targeted replacement mice to investigate the impact of APOE alleles on the murine gut microbiome. The relative abundance of bacteria from the family Ruminococacceae and related genera increased with APOE2 status. The relative abundance of the class Erysipelotrichia increased with APOE4 status, …

Effects Of Traumatic Brain Injury On The Intestinal Tract And Gut Microbiome, Anthony Desana

Theses and Dissertations--Physiology

Traumatic brain injury (TBI) initiates not only complex neurovascular and glial changes within the brain but also pathophysiological responses that extend beyond the central nervous system. The peripheral response to TBI has become an intensive area of research, as these systemic perturbations can induce dysfunction in multiple organ systems. As there are no approved therapeutics for TBI, it is imperative that we investigate the peripheral response to TBI to identify targets for future intervention. Of particular interest is the gastrointestinal (GI) system. Even in the absence of polytrauma, brain-injured individuals are at increased risk of suffering from GI-related morbidity and …

Clinical And Biological Factors Determine Spinal Cord Injury Outcomes: Liquor To Lipids, Ethan Glaser

Theses and Dissertations--Physiology

Spinal cord injuries (SCI) are debilitating and life altering events that can lead to permanent motor and sensory loss. SCI outcomes are impacted by both clinical factors such as blood alcohol content (BAC) at the time of injury as well as biological factors like the lipid-rich myelin debris that accumulates in the injury site. Both clinical and biological factors contribute to SCI recovery, impacting neuroinflammation, locomotor recovery, and histopathology. The purpose of the studies described here is to investigate the role of acute alcohol intoxication and intracellular lipid processing pathways on SCI outcomes in a rodent model.

An elevated BAC …

Polyrhythmic Pathways: Using Bimanual Coordination Research To Develop A New Framework For Practice, Performance, And Pedagogy, Christian Swafford

Theses and Dissertations--Music

This study reviews and compares percussion literature pertaining to polyrhythms and scientific literature pertaining to bimanual coordination. There exists a gap in the pedagogical approach to polyrhythms, and there is much disagreement between common instructional methods, especially when considered against the findings of several bimanual coordination studies. The purpose of this study is to reveal insight to the percussion community that the learning of polyrhythms is facilitated by the brain in novel ways, and the uniqueness of this learning process requires a rethinking of the current pedagogical approach. Percussion articles, method books, popular literature, and music scores are surveyed alongside …

Therapeutic Implications Of The Gut-Cns Axis In Promoting Recovery Following Cervical Spinal Cord Injury, Jessica Wilson

Theses and Dissertations--Neuroscience

Nearly 60% of all spinal cord injuries (SCI) occur at the cervical level. These high-level injuries can interrupt the descending respiratory pathways required for breathing. Indeed, therapies in animal studies have been successful at restoring breathing after SCI; however, these interventions appear to be more effective at chronic time points. One potential cause for this observation is the impact of the injury on the gut microbiome. Neurotrauma can induce gut dysbiosis, an imbalance of pathogenic and beneficial gut microbiota, which has previously been shown to negatively impact the central nervous system (CNS) and impair recovery. We aimed to build upon …

Calcium Imaging Of Central Amygdala Activity After Fentanyl Escalation, Samantha Malone

Theses and Dissertations--Psychology

Evidence suggests that rats given long access (LgA) sessions to self-administer (SA) opioids escalate their intake, while also showing greater withdrawal severity and drug-induced reinstatement compared to rats maintained on short access (ShA) daily SA sessions. Little is known about the neural changes that occur during opioid escalation that may impact withdrawal and relapse. Past work examining opioid SA using ShA sessions in rodents has identified the central amygdala (CeA) as an area of interest that becomes hyperactive in acute withdrawal and may be involved in the incubation of craving that occurs after protracted withdrawal. However, these studies have not …

Glia Excitation In The Cns Modulates Intact Behaviors And Sensory-Cns-Motor Circuitry, Shelby Mccubbin, Douglas A. Harrison, Robin L. Cooper

Biology Faculty Publications

Glial cells play a role in many important processes, though the mechanisms through which they affect neighboring cells are not fully known. Insights may be gained by selectively activating glial cell populations in intact organisms utilizing the activatable channel proteins channel rhodopsin (ChR2XXL) and TRPA1. Here, the impacts of the glial-specific expression of these channels were examined in both larval and adult Drosophila. The Glia > ChR2XXL adults and larvae became immobile when exposed to blue light and TRPA1-expressed Drosophila upon heat exposure. The chloride pump expression in glia > eNpHR animals showed no observable differences in adults or larvae. In …

Therapeutic Treatment With The Anti-Inflammatory Drug Candidate Mw151 May Partially Reduce Memory Impairment And Normalizes Hippocampal Metabolic Markers In A Mouse Model Of Comorbid Amyloid And Vascular Pathology, David J. Braun, David K. Powell, Christopher J. Mclouth, Saktimayee M. Roy, D. Martin Watterson, Linda J. Van Eldik

Neuroscience Faculty Publications

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, but therapeutic options are lacking. Despite long being able to effectively treat the ill-effects of pathology present in various rodent models of AD, translation of these strategies to the clinic has so far been disappointing. One potential contributor to this situation is the fact that the vast majority of AD patients have other dementia-contributing comorbid pathologies, the most common of which are vascular in nature. This situation is modeled relatively infrequently in basic AD research, and almost never in preclinical studies. As part of our efforts to develop …

Membrane Palmitoylated Protein Magu-3 Regulates The C. Elegans Locomotor Circuit Via Modulation Of Cholinergic Activity, Henry Richburg

Theses and Dissertations--Medical Sciences

Precise coordination of the activity and transmission in excitatory and inhibitory neural circuits is essential for healthy information flow. Synaptic scaffolding proteins play a key role in the regulation of circuit activity through the localization and organization of receptors, channels, and other synaptic machinery to facilitate signal transduction. Using the C. elegans motor circuit which has both cholinergic (excitatory) and GABAergic (inhibitory) inputs onto muscles, we revealed an unexplored role of a family of scaffolding molecules known as membrane palmitoylated proteins (MPPs). Here, we examined magu-3, a C. elegans ortholog within the membrane palmitoylated protein family, using GFP tagging …

Investigating The Effects Of In-Vivo Therapeutics Hypoxia Treatment Paradigms In Neurite Outgrowth Patterns, Jae Hyun Yoo

Theses and Dissertations--Medical Sciences

Spinal cord injury, specifically in the cervical C3-C4 region of the cervical spine, contributes to impaired breathing and a diminished quality of life. Therefore it is important to find effective and safe therapeutics to restore breathing function. Indeed, there are a myriad of research being performed in addition to valuable collaboration amongst different institutions. As such, inspired by a previous experiment, we decided to test our hypothesis that an enriching environment consisting of different hypoxic environments - sustained and intermittent hypoxia alongside normoxia - would result in neurite outgrowth. Moreover, we hypothesized that sustained hypoxia would result in the greatest …

An Investigation Of Hhv6'S Impact On The Cognitive Progression And Microglial Changes In An Alzheimer's Disease Cohort, Charles E. Seaks

Theses and Dissertations--Physiology

The role of herpesviruses and, more specifically, HHV6 in the development of Alzheimer’s disease (AD) and associated cognitive decline is still being investigated. High ubiquity and prevalence in the population have led to a high degree of skepticism about HHV6 as a potential contributor to cognitive decline and dementias. However, recent evidence related to another herpesvirus, herpes simplex virus 1, suggests that reactivation, not carriage, of the virus may be the key factor to explain the dissonance between the virus’ ubiquity and contributions to dementias. With that in mind, we set out to assess cases from the Sanders-Brown Center on …

Investigating Mechanisms Of Injury And Intervention In A Novel In Vitro Model Of Traumatic Brain Injury In Organotypic Hippocampal Slice Cultures, Julia Elaine Jagielo-Miller

Theses and Dissertations--Psychology

Traumatic brain injuries (TBIs) impact millions of individuals each year and can pose long term consequences. Despite numerous attempts, no medication has been approved by the FDA to treat TBIs. The causes of these failed trials are multifaceted, but in part can be attributed to the complex nature of TBIs, as well as a lack of sufficient pre-clinical data. In vitro models of TBI are an important tool to help understand the cellular changes seen following the injury, in a highly controlled environment. For the following experiments, a novel model of TBI was used to injure organotypic hippocampal slice cultures, …

Apoe Genotype And Cerebral Glucose Metabolism: A Multi-Omics Approach, Holden C. Williams

Theses and Dissertations--Physiology

Apolipoprotein E (APOE) is encoded by the APOE gene, present in humans as three main isoforms (E2, E3, and E4). E4 carriers face up to a 15-fold increased risk for developing late-onset Alzheimer’s disease (AD), while E2 carriers are protected. Understanding the risk conferred by E4 has been an extensive research focus for nearly three decades, but the exact mechanism has yet to be proven. Many studies have demonstrated attenuated roles of E4 in classical hallmarks of AD, notably amyloid processing and neurofibrillary formation, which normally present later in disease progression. How APOE influences hallmarks that present much earlier are …

Uncovering The Role Of Apoe4 On Alzheimer’S Disease-Related Neuroinflammation, Courtney Marie Kloske

Theses and Dissertations--Physiology

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by two hallmark pathologies: amyloid-beta plaques (Ab plaques) and hyperphosphorylated, aggregated tau tangles. These pathologies are typically accompanied by the presence of neuroinflammation which is primarily mediated by microglia. Interestingly, several genetic risk factors that increase the risk of AD also have direct impacts on neuroinflammation. Of interest, Apolipoprotein E (ApoE) is the largest genetic risk factor for AD. ApoE has three isoforms- E4 confers an increased risk for AD, E3 is considered the “control” phenotype, and E2 is protective against AD. E4 plays a role in virtually …

Peripheral And Central Glucose Flux In Type I Diabetes, Jelena Anna Juras

Theses and Dissertations--Neuroscience

Diabetes is a complex metabolic disorder, of which high blood glucose concentration is the primary hallmark. Type I diabetes mellitus (T1DM) is characterized by the lack of insulin production, due to a poorly understood autoinflammatory cascade. In the words of historian Barnett “Diabetes may no longer be a death sentence, but for more and more people in the 21st century, it will become a life sentence”, making it the focal point of many research groups. It is estimated that around 20 million individuals worldwide live with T1DM.

Effects of long-term chronically elevated blood glucose are not only seen in micro/macro-vascular …

Development Of Fluorescence Based Approaches To Understand Astrocyte Biology In The Context Of Nicotine And Nicotinic Receptor Activity, Surya P. Aryal

Theses and Dissertations--Chemistry

Smoking and tobacco use (STU) is a major global health problem and worldwide more than six million people die due to tobacco related diseases each year. Although majority of smokers try to quit smoking several times in their life, traditional therapeutic approaches, which focus only on neuronal cells, have a very low success rate. Understanding the effect of nicotine on glial cells, synaptic communication and blood vasculature in the brain can provide further insights on the neurobiology of substance abuse and can potentially help to design better therapeutic approaches. Glial cells are non-excitable cells in the brain which do not …

The Effect Of Optogenetically Activating Glia On Neuronal Function, Cecilia Pankau, Shelby Mccubbin, Robin L. Cooper

Biology Faculty Publications

Glia, or glial cells, are considered a vital component of the nervous system, serving as an electrical insulator and a protective barrier from the interstitial (extracellular) media. Certain glial cells (i.e., astrocytes, microglia, and oligodendrocytes) within the CNS have been shown to directly affect neural functions, but these properties are challenging to study due to the difficulty involved with selectively-activating specific glia. To overcome this hurdle, we selectively expressed light-sensitive ion channels (i.e., channel rhodopsin, ChR2-XXL) in glia of larvae and adult Drosophila melanogaster. Upon activation of ChR2, both adults and larvae showed a rapid contracture of body wall …

The Effect Of Calcium Ions On Mechanosensation And Neuronal Activity In Proprioceptive Neurons, Devan E. Atkins, Kimberly L. Bosh, Grace W. Breakfield, Sydney E. Daniels, Makayla J. Devore, Hailey E. Fite, Landys Z. Guo, Danielle K. J. Henry, Alana K. Kaffenberger, Katherine S. Manning, Tatum E. Mowery, Cecilia L. Pankau, Nyla Parker, Malina E. Serrano, Yamaan Shakhashiro, Hannah N. Tanner, Ruth. A. Ward, Aubrey H. Wehry, Robin L. Cooper

Biology Faculty Publications

Proprioception of all animals is important in being able to have coordinated locomotion. Stretch activated ion channels (SACs) transduce the mechanical force into electrical signals in the proprioceptive sensory endings. The types of SACs vary among sensory neurons in animals as defined by pharmacological, physiological and molecular identification. The chordotonal organs within insects and crustaceans offer a unique ability to investigate proprioceptive function. The effects of the extracellular environment on neuronal activity, as well as the function of associated SACs are easily accessible and viable in minimal saline for ease in experimentation. The effect of extracellular [Ca²⁺] on …

Pairwise Correlation Analysis Of The Alzheimer’S Disease Neuroimaging Initiative (Adni) Dataset Reveals Significant Feature Correlation, Erik D. Huckvale, Matthew W. Hodgman, Brianna B. Greenwood, Devorah O. Stucki, Katrisa M. Ward, Mark T. W. Ebbert, John S. K. Kauwe, The Alzheimer’S Disease Neuroimaging Initiative, The Alzheimer’S Disease Metabolomics Consortium, Justin B. Miller

Sanders-Brown Center on Aging Faculty Publications

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) contains extensive patient measurements (e.g., magnetic resonance imaging [MRI], biometrics, RNA expression, etc.) from Alzheimer’s disease (AD) cases and controls that have recently been used by machine learning algorithms to evaluate AD onset and progression. While using a variety of biomarkers is essential to AD research, highly correlated input features can significantly decrease machine learning model generalizability and performance. Additionally, redundant features unnecessarily increase computational time and resources necessary to train predictive models. Therefore, we used 49,288 biomarkers and 793,600 extracted MRI features to assess feature correlation within the ADNI dataset to determine the …

Sex Differences In Mitochondrial Function Following A Controlled Cortical Impact Traumatic Brain Injury In Rodents, Olivia J. Kalimon, Patrick G. Sullivan

Neuroscience Faculty Publications

Traumatic brain injury (TBI) is a complex disease to study due to the multifactorial injury cascades occurring after the initial blow to the head. One of the most vital players in this secondary injury cascade, and therapeutic target of interest, is the mitochondrion. Mitochondria are important for the generation of cellular energy, regulation of cell death, and modulation of intracellular calcium which leaves these “powerhouses” especially susceptible to damage and dysfunction following traumatic brain injury. Most of the existing studies involving mitochondrial dysfunction after TBI have been performed in male rodent models, leaving a gap in knowledge on these same …

Editorial: Roles Of Sleep Disruption And Circadian Rhythm Alterations On Neurodegeneration And Alzheimer's Disease, Marilyn J. Duncan, Sigrid C. Veasey, Phyllis Zee

Neuroscience Faculty Publications

No abstract provided.

Editorial: Invertebrate Neuroscience: Contributions From Model And Non-Model Species, Maria P. Fernandez, Clare C. Rittschof, Jimena A. Sierralta

Entomology Faculty Publications

No abstract provided.

White Matter Hyperintensity Volume And Location: Associations With Wm Microstructure, Brain Iron, And Cerebral Perfusion, Christopher E. Bauer, Valentinos Zachariou, Elayna R. Seago, Brian T. Gold

Neuroscience Faculty Publications

Cerebral white matter hyperintensities (WMHs) represent macrostructural brain damage associated with various etiologies. However, the relative contributions of various etiologies to WMH volume, as assessed via different neuroimaging measures, is not well-understood. Here, we explored associations between three potential early markers of white matter hyperintensity volume. Specifically, the unique variance in total and regional WMH volumes accounted for by white matter microstructure, brain iron concentration and cerebral blood flow (CBF) was assessed. Regional volumes explored were periventricular and deep regions. Eighty healthy older adults (ages 60–86) were scanned at 3 Tesla MRI using fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), …

Healthy Dietary Intake Moderates The Effects Of Age On Brain Iron Concentration And Working Memory Performance, Valentinos Zachariou, Christopher E. Bauer, Elayna R. Seago, Georgia Panayiotou, Edward D. Hall, D. Allan Butterfield, Brian T. Gold

Neuroscience Faculty Publications

Age-related brain iron accumulation is linked with oxidative stress, neurodegeneration and cognitive decline. Certain nutrients can reduce brain iron concentration in animal models, however, this association is not well established in humans. Moreover, it remains unknown if nutrition can moderate the effects of age on brain iron concentration and/or cognition. Here, we explored these issues in a sample of 73 healthy older adults (61-86 years old), while controlling for several factors such as age, gender, years of education, physical fitness and alcohol-intake. Quantitative susceptibility mapping was used for assessment of brain iron concentration and participants performed an N-Back paradigm to …